Tanzania’s Countdown to 2015: an analysis of two decades of progress and gaps for reproductive, maternal, newborn, and child health, to inform priorities for post-2015

Background Tanzania is on track to meet Millennium Development Goal (MDG) 4 for child survival, but is making insuffi cient progress for newborn survival and maternal health (MDG 5) and family planning. To understand this mixed progress and to identify priorities for the post-2015 era, Tanzania was selected as a Countdown to 2015 case study. Methods We analysed progress made in Tanzania between 1990 and 2014 in maternal, newborn, and child mortality, and unmet need for family planning, in which we used a health systems evaluation framework to assess coverage and equity of interventions along the continuum of care, health systems, policies and investments, while also considering contextual change (eg, economic and educational). We had fi ve objectives, which assessed each level of the health systems evaluation framework. We used the Lives Saved Tool (LiST) and did multiple linear regression analyses to explain the reduction in child mortality in Tanzania. We analysed the reasons for the slower changes in maternal and newborn survival and family planning, to inform priorities to end preventable maternal, newborn, and child deaths by 2030. Findings In the past two decades, Tanzania’s population has doubled in size, necessitating a doubling of health and social services to maintain coverage. Total health-care fi nancing also doubled, with donor funding for child health and HIV/AIDS more than tripling. Trends along the continuum of care varied, with preventive child health services reaching high coverage (≥85%) and equity (socioeconomic status diff erence 13–14%), but lower coverage and wider inequities for child curative services (71% coverage, socioeconomic status diff erence 36%), facility delivery (52% coverage, socioeconomic status diff erence 56%), and family planning (46% coverage, socioeconomic status diff erence 22%). The LiST analysis suggested that around 39% of child mortality reduction was linked to increases in coverage of interventions, especially of immunisation and insecticide-treated bednets. Economic growth was also associated with reductions in child mortality. Child health programmes focused on selected high-impact interventions at lower levels of the health system (eg, the community and dispensary levels). Despite its high priority, implementation of maternal health care has been intermittent. Newborn survival has gained attention only since 2005, but high-impact interventions are already being implemented. Family planning had consistent policies but only recent reinvestment in implementation. Interpretation Mixed progress in reproductive, maternal, newborn, and child health in Tanzania indicates a complex interplay of political prioritisation, health fi nancing, and consistent implementation. Post-2015 priorities for Tanzania should focus on the unmet need for family planning, especially in the Western and Lake regions; addressing gaps for coverage and quality of care at birth, especially in rural areas; and continuation of progress for child health

Tanzania's countdown to 2015: an analysis of two decades of progress and gaps for reproductive, maternal, newborn, and child health, to inform priorities for post-2015.

BACKGROUND: Tanzania is on track to meet Millennium Development Goal (MDG) 4 for child survival, but is making insufficient progress for newborn survival and maternal health (MDG 5) and family planning. To understand this mixed progress and to identify priorities for the post-2015 era, Tanzania was selected as a Countdown to 2015 case study. METHODS: We analysed progress made in Tanzania between 1990 and 2014 in maternal, newborn, and child mortality, and unmet need for family planning, in which we used a health systems evaluation framework to assess coverage and equity of interventions along the continuum of care, health systems, policies and investments, while also considering contextual change (eg, economic and educational). We had five objectives, which assessed each level of the health systems evaluation framework. We used the Lives Saved Tool (LiST) and did multiple linear regression analyses to explain the reduction in child mortality in Tanzania. We analysed the reasons for the slower changes in maternal and newborn survival and family planning, to inform priorities to end preventable maternal, newborn, and child deaths by 2030. FINDINGS: In the past two decades, Tanzania's population has doubled in size, necessitating a doubling of health and social services to maintain coverage. Total health-care financing also doubled, with donor funding for child health and HIV/AIDS more than tripling. Trends along the continuum of care varied, with preventive child health services reaching high coverage (≥85%) and equity (socioeconomic status difference 13-14%), but lower coverage and wider inequities for child curative services (71% coverage, socioeconomic status difference 36%), facility delivery (52% coverage, socioeconomic status difference 56%), and family planning (46% coverage, socioeconomic status difference 22%). The LiST analysis suggested that around 39% of child mortality reduction was linked to increases in coverage of interventions, especially of immunisation and insecticide-treated bednets. Economic growth was also associated with reductions in child mortality. Child health programmes focused on selected high-impact interventions at lower levels of the health system (eg, the community and dispensary levels). Despite its high priority, implementation of maternal health care has been intermittent. Newborn survival has gained attention only since 2005, but high-impact interventions are already being implemented. Family planning had consistent policies but only recent reinvestment in implementation. INTERPRETATION: Mixed progress in reproductive, maternal, newborn, and child health in Tanzania indicates a complex interplay of political prioritisation, health financing, and consistent implementation. Post-2015 priorities for Tanzania should focus on the unmet need for family planning, especially in the Western and Lake regions; addressing gaps for coverage and quality of care at birth, especially in rural areas; and continuation of progress for child health. FUNDING: Government of Canada, Foreign Affairs, Trade, and Development; US Fund for UNICEF; and the Bill & Melinda Gates Foundation

THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors

The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15538. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate

Discovery of common and rare genetic risk variants for colorectal cancer.

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10-8, bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.Goncalo R Abecasis has received compensation from 23andMe and Helix. He is currently an employee of Regeneron Pharmaceuticals. Heather Hampel performs collaborative research with Ambry Genetics, InVitae Genetics, and Myriad Genetic Laboratories, Inc., is on the scientific advisory board for InVitae Genetics and Genome Medical, and has stock in Genome Medical. Rachel Pearlman has participated in collaborative funded research with Myriad Genetics Laboratories and Invitae Genetics but has no financial competitive interest

Business not as usual: how multisectoral collaboration can promote transformative change for health and sustainable development.

• We present a model of enabling fac-tors for effective multisectoral collabo-ration for improvements in health and sustainable development. • Drive change: assess whether desired change is better off achieved by mul-tisectoral collaboration; drive forward collaboration by mobilising a critical mass of policy and public attention. • Define: frame the problem strategi-cally and holistically so that all sec-tors and stakeholders can see the benefits of collaboration and contri-bution to the public good• Design: create solutions relevant to context, building on existing mecha-nisms, and leverage the strengths of diverse sectors for collective impact. • Relate: ensure resources for multi-sectoral collaboration mechanisms, including for open communication and deliberation on evidence, norms, and innovation across all components of collaboration. • Realise: learn by doing, and adapt with regular feedback. Remain open to redefining and redesigning the collaboration to ensure relevance, effectiveness, and responsiveness to change. • Capture success: agree on success markers, using qualitative and quan-titative methods to monitor results regularly and comprehensively, and learn from both failures and successes to inform action and sustain gains

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The Initiative to Maximize Progress in Adolescent and Young Adult Cancer Therapy (IMPACT) Cohort Study: a population-based cohort of young Canadians with cancer

BACKGROUND: Cancer is the leading cause of disease-related death in adolescents and young adults (AYA). Annual improvements in AYA cancer survival have been inferior to those observed in children and older adults. Prior studies of AYA with cancer have been limited by their focus on patients from select treatment centres, reducing generalizability, or by being population-based but lacking diagnostic and treatment details. There is a critical need to conduct population-based studies that capture detailed patient, disease, treatment and system-level data on all AYA regardless of treatment location. METHODS/DESIGN: We will create a cohort of all AYA (aged 15–21 years) at the time of diagnosis with any malignancy between 1992 and 2011 in Ontario, Canada (n = 5,394). Subjects will be identified through the Ontario Cancer Registry and the final cohort will be expanded to include 2012 diagnoses, as these data become available. Detailed diagnostic, treatment and outcome data for those patients treated at a pediatric cancer centre will be provided by a population-based pediatric cancer registry (n = 1,030). For 15–18 year olds treated at adult centres (n = 923) and all 19–21 year olds (n = 3396), trained abstractors will collect the comparable data elements from medical records. We will link these data to population-based administrative health data that include physician billings, hospitalizations and emergency room visits. This will allow descriptions of health care access and use prior to cancer diagnosis, and during and after treatment. DISCUSSION: The IMPACT cohort will serve as a platform for addressing questions that span the AYA cancer journey. These will include determining which factors influence where AYA receive care, the impact of locus of care on the types and intensity of cancer therapy, appropriateness of surveillance for disease recurrence, access to clinical trials, and receipt of palliative and survivor care. Findings using the IMPACT cohort have the potential to lead to changes in practice and cancer policy, reduce mortality, and improve quality of life for AYA with cancer. The IMPACT data platform will be a permanent resource, accessible to researchers across Canada

THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors.

The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15538. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate

The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors.

peer reviewedThe Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.16177. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate